Clomiphene-induced LH surges and cetrorelix

The following rat pituitary cell culture experiments were carried out to find an explanation for the increased premature LH surges in stimulation protocols using clomiphene citrate (CC) and subsequent gonadotrophin with mid-cycle administration of the GnRH antagonist cetrorelix (Cetrotide(R)) in IVF cycles. Rat pituitary cells were pretreated with CC, then stimulated with GnRH with and without co-administration of different concentrations of GnRH antagonist and compared with non-CC-pretreated controls. While lower concentrations of cetrorelix suppressed LH in CC-non-pretreated cells, but not in CC-pretreated cells, higher concentrations of cetrorelix suppressed LH in both groups. CC pretreatment increased the sensitivity of the pituitary for GnRH and reduced the efficacy of subsequent GnRH antagonist. Thus, the elevated risk of premature LH surges in clinical protocols using CC, gonadotrophin and GnRH antagonist could be overcome by increasing the antagonist dose.